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“Rule of Five” Unreliable for Glaucoma

Researchers found this RNFL guideline resulted in high false positives for progression.

While looking for thinning in the retinal nerve fiber layer (RNFL) is a popular method of tracking glaucomatous progression, a recent study from the Vision, Imaging and Performance Laboratory at the Duke Eye Center found loss of ≥5μm in global RNFL thickness on spectral-domain optical coherence tomography (SD-OCT) between visits does not always mean progression. Researchers found the cumulative proportion of an intervisit gain of ≥5μm at five years suggested that only 13.2% of eyes with glaucoma had truly progressed.

The study examined 92 eyes in 49 controls and 300 eyes in 210 glaucoma subjects. Participants completed at least five standard automated perimetry and SD-OCT examinations at six-month intervals over at least two years. The false positive proportion was estimated by two methods: ≥5μm loss in controls and ≥5μm gain in glaucoma.

After five years of testing, the cumulative proportion of false positives based on ≥5μm RNFL losses between visits was 24.8% in the controls. While 40.6% of glaucoma eyes were diagnosed with progression at five years, only 15.8% would have been considered “true” progression after subtracting the cumulative proportion of false positives (40.6% - 24.8%). Researchers found that the cumulative proportion of an intervisit gain of ≥5μm at five years was 27.4% in glaucoma eyes, which suggested that only 13.2% of eyes with glaucoma had truly progressed.

The study concluded that applying the intervisit “rule of five” could result in a high cumulative proportion of false positives over time and lead to unnecessary interventions in patients whose disease is stable. Researchers call for more specific diagnostic criteria to help practitioners determine whether patients are progressing from glaucoma in order for timely and appropriate therapy escalation.